A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with CFS

[Laelia]

This is old but I'm not sure if it has been posted anywhere on here?

Am J Med. 1990 Nov;89(5):561-8.
A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome.
Lloyd A1, Hickie I, Wakefield D, Boughton C, Dwyer J.
Author information

Abstract
PURPOSE:
The chronic fatigue syndrome (CFS) is characterized by profound fatigue, neuropsychiatric dysfunction, and frequent abnormalities in cell-mediated immunity. No effective therapy is known.

PATIENTS AND METHODS:
Forty-nine patients (40 with abnormal cell-mediated immunity) participated in a randomized, double-blind, placebo-controlled trial to determine the effectiveness of high-dose intravenously administered immunoglobulin G. The patients received three intravenous infusions of a placebo solution or immunoglobulin at a dose of 2 g/kg/month. Assessment of the severity of symptoms and associated disability, both before and after treatment, was completed at detailed interviews by a physician and psychiatrist, who were unaware of the treatment status. In addition, any change in physical symptoms and functional capacity was recorded using visual analogue scales, while changes in psychologic morbidity were assessed using patient-rated indices of depression. Cell-mediated immunity was evaluated by T-cell subset analysis, delayed-type hypersensitivity skin testing, and lymphocyte transformation with phytohemagglutinin.

RESULTS:
At the interview conducted by the physician 3 months after the final infusion, 10 of 23 (43%) immunoglobulin recipients and three of the 26 (12%) placebo recipients were assessed as having responded with a substantial reduction in their symptoms and recommencement of work, leisure, and social activities. The patients designated as having responded had improvement in physical, psychologic, and immunologic measures (p less than 0.01 for each).

CONCLUSION:
Immunomodulatory treatment with immunoglobulin is effective in a significant number of patients with CFS, a finding that supports the concept that an immunologic disturbance may be important in the pathogenesis of this disorder.

https://www.ncbi.nlm.nih.gov/pubmed/2146875

 

[M Paine]

Full Text - http://sci-hub.cc/10.1016/0002-9343(90)90173-b

 

[AndyPR]

As far as I can see, it's only be talked about on PR as part of this blog post, http://forums.phoenixrising.me/index.php?threads/parvovirus-b19-in-an-icosahedral-nutshell.22909/

 

[Esther12]

Looks like a null follow up from Lloyd in 1997:

https://www.ncbi.nlm.nih.gov/pubmed/9236484

I thought that there was another null result inbetween those two as well, but cannot find it, so maybe I was wrong.

 

[Hutan]

Peterson PK, Shepard J, Macres M, et al. A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome. Am J Med 1990; 89: 554-560.

Lloyd A, Hickie I, Wakefield D, et al. A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome. Am J Med 1990; 89: 561-568.

Rowe KS. Double-blind randomized controlled trial to assess the efficacy of intravenous gammaglobulin for the management of chronic fatigue syndrome in adolescents. J Psychiatr Res 1997; 133-147.

Vollmer-Conna U, Hickie I, Hadzi-Pavlovic D, et al. Intravenous immunoglobulin is ineffective in the treatment of patients with chronic fatigue syndrome. Am J Med 1997; 103: 38-43.


I think Kathy Rowe's study in 1997 found a positive result of IVIg for adolescents. I was surprised when I heard about it that it wasn't followed up. But if there was a context of follow-up studies in adults finding null results then that might explain it.

 

[charles shepherd]

From the MEA purple book (2017 edition):

Treatment section: Immunomodulatory drugs

· Intravenous injections of pooled human immunoglobulin have been assessed in five RCTs. Three reported benefits (DuBois 1986 – for “chronic mononucleosis syndrome”; Lloyd et al 1990; Rowe KS 1997) whereas two found no benefit (Peterson et al 1990; Vollmer-Conna et al 1997). There is no published evidence to support the use of intramuscular injection of human immunoglobulin or low-dose intravenous immunoglobulin in research-defined CFS. Immunoglobulin has also been reported to be of benefit in parvovirus-induced ME/CFS (Kerr et al 2003).

NB: The NICE guideline on ME/CFS does not recommend the use of any immunomodulatory treatment for ME/CFS

So, given the very speculatory nature of this form of treatment, it is unlikely to be prescribed on the NHS here in the UK

CS

 

[Marky90]

From the MEA purple book (2017 edition):

Treatment section: Immunomodulatory drugs

· Intravenous injections of pooled human immunoglobulin have been assessed in five RCTs. Three reported benefits (DuBois 1986 – for “chronic mononucleosis syndrome”; Lloyd et al 1990; Rowe KS 1997) whereas two found no benefit (Peterson et al 1990; Vollmer-Conna et al 1997). There is no published evidence to support the use of intramuscular injection of human immunoglobulin or low-dose intravenous immunoglobulin in research-defined CFS. Immunoglobulin has also been reported to be of benefit in parvovirus-induced ME/CFS (Kerr et al 2003).

NB: The NICE guideline on ME/CFS does not recommend the use of any immunomodulatory treatment for ME/CFS

So, given the very speculatory nature of this form of treatment, it is unlikely to be prescribed on the NHS here in the UK

CS

We tried getting someone interested in IVIG in Norway, but alas. It is however prematurely rejected, and should be researched again with strict criteria and objective measures.

 

[Research 1st]

We tried getting someone interested in IVIG in Norway, but alas. It is however prematurely rejected, and should be researched again with strict criteria and objective measures.

Exactly and well said.

Until it means something medically to be an ME CFS patient in any study (biomarkers), unless we use as strict criteria as possible until then (ME-ICC), potential therapies like IVIG are wasted via negative studies that may fail, due to the heterogenous cohort issue.

Hence 1 study say this works, 3 says it doesn't and the idea gets dropped in favour of useless CBT GET as that's cheap and helps place responsibility of recovery on the patient, not the state.

Anti Science Governments love anything that demonstrates ME CFS diagnosese have real serious organic diseases inside them, which is why they love Fukuda CFS (PEM not required!) and British F48.0 psych Chronic Fatigue (active depression and past mental illness permitted at time of CFS diagnosis!).

So naturally from this issue of no test confirming the diagnosis of ME CFS, you get 30 'CFS' patients in a study, and find zero response from IVIG vs placebo because the patients tested, no one even knows if the have ME or not.